NCT05570305

Zibotentan and Dapagliflozin in Patients With Type 2 Diabetes and Elevated Albuminuria

A Study to Assess the Effects of the Endothelin Receptor Antagonist Zibotentan and the SGLT2 Inhibitor Dapagliflozin in Patients With Type 2 Diabetes and Elevated Albuminuria: a Randomized Double Blind Cross-Over Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (actual)
• Sponsor: University Medical Center Groningen · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The aim of this study is to test the hypothesis that the effects on albuminuria of combination treatment with the endothelin receptor antagonist zibotentan and SGLT2i dapagliflozin are complimentary and additive while the fluid retaining effects of zibotentan can be mitigated by dapagliflozin.

Detailed description

A double-blind randomized placebo controlled cross-over study will be conducted in male and female subjects with type 2 diabetes aged between 18 and 75 years, urinary albumin:creatinine ratio (UACR) levels between 100 and 3500 mg/g, and an eGFR ≥ 30 ml/min/1.73m2 will be enrolled. Patients with type 1 diabetes or non-diabetic kidney disease will be excluded. The study will consist of a screening visit, a 4-week (up to a maximum of 16-weeks) run-in phase for those subjects not on stable ACEi/ARB treatment. Subjects will be randomly assigned to one of two treatment orders. Each treatment order consists of three treatment periods, separed separated by 4-week wash-out period. Treatment period 1 and 2 take four weeks. The third treatment period last 6 weeks. Participants will be randomized to treatments in addition to receiving background local standard of care (SoC) therapy as follows: 1. Zibotentan 1.5 mg once daily + Dapagliflozin 10 mg once daily. 2. Zibotentan 1.5 mg once daily. 3. Dapagliflozin 10 mg once daily. 4. Placebo once daily.

Conditions

• Chronic Kidney Diseases

Interventions

Type	Name	Description
DRUG	Zibotentan	Zibotentan 1.5 mg once per day as a hard capsule.
DRUG	Dapagliflozin	Dapagliflozin 10 mg once per day as a tablet.
DRUG	Placebo	Matching placebo.
DRUG	Dapagliflozin and Zibotentan	Dapagliflozin 10 mg once per day as a tablet in combination with zibotentan 1.5 mg once per day as a hard capsule.

Timeline

• Start date: 2022-10-06
• Primary completion: 2025-03-05
• Completion: 2025-03-05
• First posted: 2022-10-06
• Last updated: 2025-04-30

Locations

7 sites across 5 countries: United States, Canada, Denmark, Netherlands, United Kingdom

Regulatory

• FDA-regulated drug study